Development and function of human innate immune cells in a humanized mouse model


Mice repopulated with human hematopoietic cells are a powerful tool for the study of human hematopoiesis and immune function in vivo. However, existing humanized mouse models cannot support development of human innate immune cells, including myeloid cells and natural killer (NK) cells. Here we describe two mouse strains called MITRG and MISTRG, in which human versions of four genes encoding cytokines important for innate immune cell development are knocked into their respective mouse loci. The human cytokines support the development and function of monocytes, macrophages and NK cells derived from human fetal liver or adult CD34(+) progenitor cells injected into the mice. Human macrophages infiltrated a human tumor xenograft in MITRG and MISTRG mice in a manner resembling that observed in tumors obtained from human patients. This humanized mouse model may be used to model the human immune system in scenarios of health and pathology, and may enable evaluation of therapeutic candidates in an in vivo setting relevant to human physiology.

DOI: 10.1038/nbt.2858

Extracted Key Phrases

1 Figure or Table

Showing 1-10 of 47 references
Showing 1-10 of 51 extracted citations
Citations per Year

304 Citations

Semantic Scholar estimates that this publication has received between 145 and 564 citations based on the available data.

See our FAQ for additional information.